The public health and economic burden imposed by mosquito-borne diseases on the developing world, and especially Africa, is enormous. Malaria accounts for the largest portion of global mosquito-borne disease morbidity and mortality. There is an urgent need for novel vector control tools that reduce malaria transmission by mosquitoes in distinct ways from traditional insecticides, including tools that have new molecular targets in mosquitoes, new modes of delivery to the mosquito, and tools that can target transmission by vectors not well- controlled by insecticide-treated nets or indoor residual spraying. To be maximally effective in resource- constrained environments of the developing world, such tools must also be able to integrate with existing malaria control interventions and existing human health infrastructures. Our broad hypothesis is that ivermectin used in human de-worming campaigns in African villages, and which we have shown can disrupt malaria parasite transmission in Senegalese villages, could serve as one of these promising new tools. Ivermectin is an oral drug, already given by mass administration to humans in the developing world for onchocerciasis control, and malaria vectors can ingest and be killed by this drug when they bite humans after these mass drug administrations. Our data suggests that more frequent administrations of ivermectin in malaria-endemic communities would result in sustained reductions in malaria parasite transmission. To get to this goal, a thorough examination of the ivermectin effects against malaria vectors in the field and laboratory is necessary. We propose two specific aims: Aim 1: Perform field population studies in Senegal on the effects of ivermectin ingested by wild malaria vectors. Aim 2: Perform laboratory and modeling studies on the effects ivermectin may have on mosquitoes and malaria parasite transmission. PUBLIC HEALTH RELEVANCE: This project proposes to understand how the drug ivermectin can affect the survival of African malaria vectors and interrupt malaria parasite transmission in Africa. The project is intended to lay the scientific foundation for using ivermectin as a new malaria control tool.